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Diss Factsheets

Administrative data

Description of key information

LD50 Oral gavage (rat) > 5000 mg/kg bw (similar to OECD 401, Ciba-Geigy 1981)
LD50 Inhalation (rat) > 1.81 mg/L (aerosol with 45% particles of less than 3 µm in diameter, similar to OECD 403, Ciba-Geigy 1978)
LD50 Dermal (rat) > 2000 mg/kg bw (OECD 402, GLP, Ciba-Geigy 1992)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 18, 1981 - December 2, 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline with acceptable restriction (limited reporting: purity of the test substance not reported)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
limited reporting
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Tif: RAIf (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 7-8 weeks
- Mean weight at study initiation: males ca. 181±4.5 g, females ca. 165±10.6 g
- Fasting period before study: yes, overnight
- Housing: 5 per cage
- Diet (e.g. ad libitum): rat food (NAFAG No. 890, NAFAG, Gossau)
- Water (e.g. ad libitum): drinking water
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2
- Humidity (%): 55±10
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE (polyethyleneglycol 400)
- Amount of vehicle (if gavage): 20 ml/kg bw
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Immediately after administration, clinical signs were observed at hourly intervals till 5 hrs and daily thereafter. Body-weights were recorded immediately prior to dosing (control weights) and at 7 and 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
no mortalities were observed
Clinical signs:
other: Slight sedation and exophthalmos were observed till 5 h post administration. Exophthalmos was also observed from days 8-12 post administration. Slight dyspnoea was observed till day 13 post administration. Slight to moderate ruffled fur was observed till
Gross pathology:
No compound related gross organ changes were observed.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Conclusions:
The acute oral LD50 of the test material in rats of both sexes observed over a period of 14 days was found to be greater than 5000 mg/kg bw.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline, acceptable with restrictions (Body weight was not determined after 7 days observation, only after 14 days)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
Body weight was not determined after 7 days observation, only after 14 days. Not all particles within respirable range of rats.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Tif. RAI
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited, Breeding unit
- Weight at study initiation: 227-244 g
- Diet (e.g. ad libitum): rat food, NAFAG, Gogsau SG
- Water (e.g. ad libitum): drinking water
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±1
- Humidity (%): 50±5
- Photoperiod (hrs dark / hrs light): 14/10
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Method of holding animals in test chamber: For inhalation the rats were kept in separate PVC tubes positioned radially around the exposure chamber such that snout and nostrils of the animals only were exposed to the aerosol.
- System of generating particulates/aerosols: The aerosol was generated by injecting the solid test material with the help of a "Grafix Exaktomat Injector" into an air stream which was discharged into the exposure chamber through a nozzle under a pressure of 2 atm. at a rate of 20 L/min.
- Method of particle size determination: The size distribution of the particles was measured with a Cascade Impactor with Selectron filters of 25 mm diameter and with a pore size of 0.2 µm at an air flow rate of 17.5 L/min.
- Temperature, humidity in air chamber: 27-28 °C, 19-21 %

TEST ATMOSPHERE
- Brief description of analytical method used: The concentration and the particle size distribution of the aerosol in the vicinity of the animals were monitored at 1 hour intervals throughout the aerosol exposure. The concentration was determined gravimetrically.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 7-12% of the test atmosphere were >7 µm, 38-45 % were 1-3 µm, 32-45 % were 3-7 µm, and 4-15 % were 0-1 µm
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
500, 1025 and 1811 mg/m3 (0.5, 1.025 and 1.811 mg/L)
No higher concentrations possible.
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Physical condition and incidence of death were monitored throughout an observation period of 14 days. Body weight only before treatment and at 14 days.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1.81 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: 45% less than 3 µm; no higher concentrations were possible.
Mortality:
no mortalities occurred
Clinical signs:
other: Exophthalmos, ruffled fur and ventral body position were observed.
Body weight:
Animals gained normal body weight.
Gross pathology:
No substance related gross organ changes were observed.
Interpretation of results:
not classified
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
1 800 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study with GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Remarks:
CIBA-GEIGY Limited, Short-term Toxicology
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Tif: RAI F (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited, Animal Production
- Mean weight at study initiation: males 261±10.0 g (247-274 g), females 231±13.7 g (211-244 g)
- Diet (e.g. ad libitum): Rat diet (NAFAG 890 Tox, NAFAG, Gossau)
- Water (e.g. ad libitum): drinking water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2
- Humidity (%): 55±10
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
CMC (carboxymethyl cellulose)
Details on dermal exposure:
TEST SITE
- % coverage: 10

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with lukewarm water
- Time after start of exposure: 24 h

VEHICLE
- Amount(s) applied (volume or weight with unit): 4 g (corresponding approximately to 4 ml)
- Concentration (if solution): 0.5 % (w/v) carboxymethylcellulose in 0.1 % (w/v) aqueous polysorbate 80
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality was observed twice daily and once on weekends. Signs and symptoms were observed daily. Body weight was determined immediately before application and on days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
no mortalities were observed
Clinical signs:
other: Piloerection and hunched posture were seen, being common symptoms in acute dermal tests. The animals recovered within 2 days.
Gross pathology:
At autopsy, a scurfy ear was noticed in one male. No deviations from normal morphology were found in the remaining animals.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Conclusions:
Based on the results, the test substance does not require any classification.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Oral exposure route:

In the key study (CIBA-GEIGY, 1981) performed similar to OECD guideline 401, a group of 10 rats (males and females) were orally administered with a single dose of 5000 mg/kg bw and observed for 14 days. No mortalities were observed. Clinical signs included slight sedation, dyspnoea, exophthalmos, ruffled fur and curved body position. All signs were reversible within 14 days of observation period. LD50 for male and female rats was reported to be > 5000 mg/kg bw. The results were supported by two other studies (JR GEIGY 1964), where a group of 10 rats (males and females) were orally administered with 2 or 3 application of test substance (equivalent to 10000 and 15000 mg/kg bw) at intervals of 5 h and observed for 8 days. No mortalities were observed. Signs like drowsiness and dullness were observed.

In another study (CIBA-GEIGY, 1962), rats were given the following doses by stomach tube: 1000, 2150, and 4640 mg/kg bw. Two rats, one male and one female, were used at each level. After seven days the 4640 mg/kg bw level was expanded to 10 animals. All surviving animals were kept for a 14-day observation period. There were no deaths at the two lower levels and only two out of 10 animals died at 4640 mg/kg bw dose level. One death occurred at one hour and the other nine days after dosing. Signs of toxicity consisted of unsteadiness, decreased activity and a sleepy appearance immediately after dosing. All animals appeared normal at 24 hours.

Taking the presented data into consideration (the results of former 3 studies were used for assessment), the test material is considered practically nontoxic to the rat by oral route of administration.

 

Inhalation exposure route:

In the key study performed similar to the guideline 403, rats were exposed to the test substance aerosols at analytical concentrations of 0.5, 1.025 and 1.811 mg/L for 4 hours (CIBA-GEIGY, 1978). The particle size distribution of the aerosol was as follows: 7-12% were >7 µm, 38-45 % were 1-3 µm, 32-45 % were 3-7 µm, and 4-15 % were 0-1 µm in diameter. No mortalities occurred and clinical sigs included exophthalmos, ruffled fur and ventral body position, and the LC50 for male/female was determined to be > 1.811 mg/l. The results were supported by another study (CIBA-GEIGY, 1973) where a group of rats (9 males and 9 females) were once exposed for 4 h to the test substance aerosols at concentrations of 0.667 mg/l and observed for 7 days. No mortalities occurred and clinical sigs included dyspnoea, trismus, lateral position and slight apathy.

 

Dermal exposure route:

The key study is a limit dose test with rats performed according to guideline with GLP (CIBA-GEIGY, 1992). Twenty-four hours of dermal exposure to 2000 mg/kg bw under semi-occlusive conditions resulted in no mortalities. The signs included piloerection and hunched posture was seen, being common symptoms in acute dermal tests. The animals recovered within 2 days. These results were supported by another study (CIBA-GEIGY 1962) where rabbits were exposed to 200, 632, and 2000 mg/kg bw under occlusive conditions for 24 h. No mortalities or signs of toxicity were observed during 14 days observation period.


Justification for selection of acute toxicity – oral endpoint
most recent study report

Justification for selection of acute toxicity – inhalation endpoint
most recent study report

Justification for selection of acute toxicity – dermal endpoint
GLP-compliant guideline study

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for acute oral, dermal and inhalation toxicity under Directive 67/548/EEC, as amended for the 28th time in Directive 2001/59/EC.

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for acute oral, dermal and inhalation toxicity under Regulation (EC) No. 1272/2008.